Acetic Acid → Racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,4,5-trimethylpiperazine

HRID 1011251Notes

Reaction equation

HRID 1011251 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][C@@H:15]([CH3:17])[NH:14][CH2:13][C@@H:12]1[CH3:18].C=O.[BH3-][C:22]#N.[Na+].C(O)(=O)C>C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][C@@H:15]([CH3:17])[N:14]([CH3:22])[CH2:13][C@@H:12]1[CH3:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57664344Racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazine

Product 1

HCID 57664351Racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,4,5-trimethylpiperazineYield 100%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Racemic-1-(2-Fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazine (5.71 g, 24.3 mmol) and formalin (24 mL) are dissolved in 70 mL of acetonitrile. The solution is cooled to 0° C. and 2.44 g of NaBH3CN (38.8 mmol) is added in small portions. Acetic acid (2 mL) is added until no further effervescence is observed. The crude reaction mixture is then filtered through a thick plug of silica gel that is rinsed with 10% MeOH in CH2Cl2. Concentration in vacuo gives a yellow solid that is further purified by addition of ethyl acetate and filtration. Concentration in vacuo of the filtrate gave 6.1 g of racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,4,5-trimethylpiperazine as an off-white solid (24.3 mmol, 100%). 1H NMR (300 MHz, CDCl3) δ 1.04 (d, J=4.9 Hz, 1H), 1.07 (d, J=5.2 Hz, 1H), 2.20 (dd, J=11.5, 8.8 Hz, 1H), 2.32 (s, 3H), 2.41-2.50 (m, 1H), 2.65 (dd, J=11.6, 8.9 Hz, 1H), 2.90 (dd, J=11.5, 3.3 Hz, 1H), 3.25 (dd, J=11.8, 3.0 Hz, 1H), 3.44-3.53 (m, 1H), 7.10 (t, J=8.5 Hz, 1H), 7.90 (dd, J=11.5, 2.7 Hz, 1H), 7.95-8.00 (m, 1H). LCMS-ESI (m/z): calcd for C13HBFN3O2, 267.14; [M+H]+ found, 268.2.

Workup

  1. customThe crude reaction mixture
  2. filtrationis then filtered through a thick plug of silica gel that
  3. washis rinsed with 10% MeOH in CH2Cl2
  4. concentrationConcentration in vacuo
  5. customgives a yellow solid
  6. filtrationthat is further purified by addition of ethyl acetate and filtration
  7. concentrationConcentration in vacuo of the filtrate

Sources & evidence

ORD record
ord-5a86af9eed5946adb6875c5a160aa4ca
Source dataset
uspto-grants-2011_07
Patent number
US07977352B2

Reaction notes

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